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Title: Multiple N-methylation by a designed approach enhances receptor selectivity. Author: Chatterjee J, Ovadia O, Zahn G, Marinelli L, Hoffman A, Gilon C, Kessler H. Journal: J Med Chem; 2007 Nov 29; 50(24):5878-81. PubMed ID: 17973471. Abstract: An unselective cyclic peptide integrin ligand was sequentially N-methylated by a designed approach, where only the externally oriented (solvent exposed) amide bonds were N-methylated. The N-methylation resulted in tremendous enhancement in selectivity among the different integrin receptor subtypes (alpha5beta1, alphavbeta3, and alphaIIbbeta3). Conformational and docking studies were performed, which suggested that the receptor selectivity is principally caused by reduced backbone flexibility due to N-methylation.[Abstract] [Full Text] [Related] [New Search]